positive regulation of epidermal growth factor receptor signaling pathway

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity. [GOC:go_curators]

The positive regulation of epidermal growth factor receptor (EGFR) signaling pathway is a complex process involving multiple steps, from the initial binding of EGF to the receptor to the activation of downstream signaling cascades that ultimately lead to cell growth, proliferation, and survival. Here's a detailed breakdown of the process:

**1. Ligand Binding and Receptor Dimerization:**
- The process begins with the binding of EGF, a growth factor, to its receptor, EGFR.
- This binding triggers a conformational change in the EGFR molecule, causing it to dimerize (form a pair) with another EGFR molecule.
- This dimerization is crucial for the activation of the receptor's intrinsic tyrosine kinase activity.

**2. Autophosphorylation and Activation:**
- Once dimerized, EGFRs undergo autophosphorylation, meaning they phosphorylate (add phosphate groups) to specific tyrosine residues on their own cytoplasmic tails.
- These phosphorylation events serve as docking sites for a variety of intracellular signaling proteins, including adaptor proteins, kinases, and phosphatases.

**3. Signaling Cascades:**
- The activated EGFR initiates a series of intracellular signaling cascades.
- Key downstream pathways include:
- **Ras-Raf-MEK-ERK pathway:** This pathway leads to the activation of mitogen-activated protein kinases (MAPKs), which regulate gene expression and cell proliferation.
- **PI3K-AKT pathway:** This pathway promotes cell survival and growth by inhibiting apoptosis (programmed cell death) and activating protein synthesis.
- **PLCγ pathway:** This pathway contributes to the activation of calcium signaling pathways, which regulate diverse cellular processes.

**4. Feedback Regulation:**
- The EGFR signaling pathway is tightly regulated by a complex network of positive and negative feedback loops.
- Positive feedback loops amplify the signal, while negative feedback loops dampen the signal to prevent excessive activation.
- For example, the activated EGFR can phosphorylate and activate a protein called c-Cbl, which acts as an E3 ubiquitin ligase, leading to the ubiquitination and subsequent degradation of EGFR, thus attenuating the signal.

**5. Termination of Signaling:**
- Eventually, the EGFR signaling is terminated through various mechanisms, including receptor internalization (endocytosis) and degradation.
- Once internalized, EGFR can be targeted for degradation in lysosomes, thus shutting down the signal.

**Overall, the positive regulation of EGFR signaling pathway is a highly regulated process involving multiple steps, from ligand binding and receptor activation to downstream signaling cascades and termination of the signal. This pathway plays crucial roles in diverse cellular processes, including cell growth, proliferation, differentiation, and survival. Its dysregulation is implicated in various diseases, including cancer.**'
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Proteins (10)

Compounds (1,053)